title: Human placental trophoblasts confer viral resistance to recipient cells.
abstract: Placental trophoblasts form the interface between the fetal and maternal environments and serve to limit the maternal-fetal spread of viruses. Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of viruses and, importantly, confer this resistance to nonplacental recipient cells by exosome-mediated delivery of specific microRNAs (miRNAs). We show that miRNA members of the chromosome 19 miRNA cluster, which are almost exclusively expressed in the human placenta, are packaged within trophoblast-derived exosomes and attenuate viral replication in recipient cells by the induction of autophagy. Together, our findings identify an unprecedented paracrine and/or systemic function of placental trophoblasts that uses exosome-mediated transfer of a unique set of placental-specific effector miRNAs to directly communicate with placental or maternal target cells and regulate their immunity to viral infections.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delorme-Axford
authors.forename: Rogier B
authors.initials: RB
authors.lastname: Donker
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Mouillet
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Chu
authors.forename: Avraham
authors.initials: A
authors.lastname: Bayer
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Saumendra N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Morelli
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Coyne
mesh_terms: D000704:Analysis of Variance; D001343:Autophagy / Q000235:genetics*; D002478:Cells, Cultured; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D060467:Disease Resistance / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000235:genetics / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000821:virology*; D014777:Virus Diseases / Q000635:transmission*
chemical_list: C546349:MIRN517 microRNA, human; D035683:MicroRNAs; D049452:Green Fluorescent Proteins
keywords: C19MC; miR-517-3p; primary human trophoblasts